Evidence suggests that there are compensatory changes in energy expenditure (EE) in response to periods of altered energy balance, which may be pronounced in older adults. Inducing an energy deficit by exercise is an important strategy to treat obesity;however, it is not known whether there is an optimal exercise prescription that minimizes potential compensatory changes in EE. Moreover, the physiological mechanisms underlying such changes in response to acute and chronic energy deficits induced by exercise are not known. This application proposes to use the state-of-the-art techniques to determine whether total and individual components of EE respond differently to negative energy balance induced by exercise of different prescriptions in older women, and to begin to examine its underlying physiological mechanisms. The Mentored (K99) Phase are: 1) to master, and obtain additional experience in, techniques for measuring total daily EE (using doubly-labeled water) and its components (resting metabolic rate, thermic effect of feeding via indirect calorimetry, and non-exercise activity thermogenesis using the Physical Activity Monitoring System), and laboratory assays for quantifying selected factors associated with regulation of EE;2) to use these methods to determine whether, in older women, EE responses to acute energy balance challenges, induced by separate bouts of aerobic exercise at two different intensities, are different. The overall goal of the Independent (ROO) Phase is to determine whether older women experience greater EE compensation in response to chronic exercise at a higher- than a lower-dose. The proposed study will be a direct extension and application of the knowledge and skills learned in the K99 phase. Women (60-75 yrs) will be randomized to two 16-week aerobic exercise programs of 8 or 14 kcal/kg body weight (weekly), to determine whether there will be differential changes in: 1) total daily EE and its components, and 2) aforementioned energy regulatory factors. We will also utilize the study design to obtain information on whether, in older women, there are differential improvements in outcomes related to cardiometabolic diseases. RELEVANCE (See instructions): Results of the proposed studies will help identify the optimal exercise prescription for treating obesity, and thus, will lead to more effective treatment options for increased adiposity with age.